Abstract 1027: Bcl-2 protected HNSCC cells from dasatinib-induced apoptosis

Abstract

Abstract Introduction: Head and neck squamous cell carcinoma (HNSCC) is a worldwide prevalent cancer with aggressive clinical courses and dismal outcomes. Incorporation of cetuximab, an antibody against epidermal growth factor receptor, had led to advance of treatment, but showed a modest efficacy. Therefore, new treatment for HNSCC is needed. Dasatinib, a Bcr-Abl and Src inhibitor, approved for treatment of chronic myeloid leukemia, was demonstrated to have activities for solid tumors. Here, we report the differential sensitivity of dasatinib for HNSCC cells and identify the possible molecular events. Material and method: HNSCC cells including Ca9-22, HSC3, UMSCC1, FaDu, and SAS were treated with dasatinib. Cell viability, apoptosis, and underlined signal transduction were evaluated by MTT assay, flow cytometry and Western blotting, respectively. Results: Five HNSCC cells treated with dasatinib displayed differential sensitivities. Ca9-22 and HSC3 cells are the most sensitive cells in response to dasatinib and showed significant growth inhibition and apoptosis. In contrast, FaDu and SAS cells are resistant to dasatinib-induced growth inhibition and apoptosis. UMSCC1 cells showed intermediate sensitivity to dasatinib; their growth was inhibited without induction of apoptosis. Src inhibition (Y416 dephosphorylation) was observed in all 5 cells treated with dasatinib. The growth inhibition of Ca9-22, HSC3, and UMSCC1 cells was correlated with inhibition of Akt and Erk activities, which is not observed in SAS and FaDu cells. In addition, anti-apoptotic protein bcl-2 was increased in UMSCC1, FaDu, and SAS cells, but decreased in Ca9-22 and HSC3 cells. Therefore, the increases of bcl-2 in UMSCC1 may protect cells from dasatinib-induced apoptosis. Conclusion: Bcl-2 plays a crucial role in dasatinib-induced apoptosis in HNSCC cells, providing a new therapeutic approach to target bcl-2 in HNSCC treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1027. doi:10.1158/1538-7445.AM2011-1027